The enteric nervous system (ENS) is the largest and most complex region of the PNS. It is the only peripheral region that can mediate reflex activity in the absence of input from the CNS. The ENS is thus an independent neural entity that has been likened to a second brain. Indeed, its structure and neurochemical content resemble those of the brain. Despite its neurobiological sophistication, which has been known for almost a century, the ENS is just emerging from a long period of scientific neglect. Its rediscovery has generated excitement, not only in the scientific community, but also among medical practitioners, who are swamped by the untreatable problems of patients with the functional bowel syndrome. The ENS has also become a major focus of research in developmental neurobiology, in part because great progress has been made in understanding gene expression in enteric neuronal development, and in part because the pathogenesis of congenital defects of the ENS can now be understood. The proposed Keystone Conference on the ENS is thus well timed and almost unique. The acquisition of new information is rising exponentially. In bringing together morphologists, physiologists, molecular biologists, developmental biologists, immunologists, pharmacologists, and clinicians, the conference will take advantage, for the first time, of the congruence of disciplines for which the ENS has become important. The conference will begin with recent progress in identifying individual enteric neurons and the microcircuits responsible for intrinsic enteric sensation, integration, and reflex activity. Also to be considered will be the complex interactions between the brain and the gut, the physiology and pharmacology of enteric neurotransmitters and their receptors, including the controversial role played by NO, and the function, development, and innervation of the enteric pacemaker, the Interstitial Cell of Cajal. Considerable time will be devoted to the genes and neuronal development as well as to the role(s) played by mutations of these genes in the pathogenesis of disease. Finally, basic-clinical sessions will attempt to related the newly expanded knowledge of the ENS to the problems faced by clinicians who must treat the bowel when it malfunctions. Formal sessions will be supplemented by posters and informal workshops. A major effort will be made to attract young investigators to the meeting and to get them to interact with senior scientists who can serve as advisors and role models.